Despite the central role the corpus luteum plays in endocrine events necessary for implantation and maintenance of early pregnancy, our knowledge of the factors which regulate the growth and differentiation of the primate corpus luteum is limited. Since endothelial cells are the major cell type (equal to or more than 50%) within the corpus luteum and because the microvasculature is critical to normal function of this endocrine gland, elucidating what regulates the proliferation and differentiation of the luteal endothelial cells is critical for understanding what controls luteal function. The proposed studies will investigate the interaction of luteal endocrine and endothelial cells via vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR). Studies will identify sites of VEGF production and receptor expression in periovulatory follicles and in luteal tissue via immunocytochemical and mRNA analyses. The forms and relative levels of VEGF mRNA and protein expressed by follicular and luteal tissue will be determined by reverse transcriptase-polymerase chain reaction (RT-PCR), ribonuclease (RNase) protection assay and western analysis, respectively. The type(s) of VEGF receptors and levels of mRNA in ovarian tissues will be determined by RT-PCR and RNase protection assay. Lastly, pituitary gonadotropin regulation of VEGF production by granulosa cells will be examined by in vivo and in vitro techniques. These studies will provide new, basic information on the angiogenic process within the primate corpus luteum which could lead to innovative methods of contraception and pregnancy termination.